Perspective

Analysis of nanoparticle delivery to tumours

  • Nature Reviews Materials 1, Article number: 16014 (2016)
  • doi:10.1038/natrevmats.2016.14
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Abstract

Targeting nanoparticles to malignant tissues for improved diagnosis and therapy is a popular concept. However, after surveying the literature from the past 10 years, only 0.7% (median) of the administered nanoparticle dose is found to be delivered to a solid tumour. This has negative consequences on the translation of nanotechnology for human use with respect to manufacturing, cost, toxicity, and imaging and therapeutic efficacy. In this article, we conduct a multivariate analysis on the compiled data to reveal the contributions of nanoparticle physicochemical parameters, tumour models and cancer types on the low delivery efficiency. We explore the potential causes of the poor delivery efficiency from the perspectives of tumour biology (intercellular versus transcellular transport, enhanced permeability and retention effect, and physicochemical-dependent nanoparticle transport through the tumour stroma) as well as competing organs (mononuclear phagocytic and renal systems) and present a 30-year research strategy to overcome this fundamental limitation. Solving the nanoparticle delivery problem will accelerate the clinical translation of nanomedicine.

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Acknowledgements

The authors thank all authors of the studies that were surveyed for providing additional information on request to calculate the nanoparticle delivery efficiencies (Supplementary information S1 (table)).The authors thank M. Samarakoon and A. Göpferich for fruitful discussions. The authors also thank S. Patel, M. Chalsev, A. Mahmood, J. D. Mora, and Y. Y. Chen for creating the database system. W.C.W.C. acknowledges the Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council (NSERC), and Prostate Cancer Canada for supporting his research program. H.F.D. acknowledges financial support from the US National Institutes of Health (NIH) grant P01 CA92644 and by a contract from the National Foundation for Cancer Research. S.O. acknowledges the Japan Society for the Promotion of Science (JSPS) for a Research Fellowship (PD, No. 5621) and the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan for a Grant-in-Aid for Young Scientists (B) (No. 26820356).

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Affiliations

  1. Stefan Wilhelm, Anthony J. Tavares, Qin Dai, Seiichi Ohta, Julie Audet and Warren C. W. Chan are at the Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College St, Toronto, Ontario M5S 3G9, Canada.

    • Stefan Wilhelm
    • , Anthony J. Tavares
    • , Qin Dai
    • , Seiichi Ohta
    • , Julie Audet
    •  & Warren C. W. Chan
  2. Julie Audet and Warren C. W. Chan are at the Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College St, Toronto, Ontario M5S 3E1, Canada.

    • Julie Audet
    •  & Warren C. W. Chan
  3. Warren C. W. Chan is at the Departments of Chemistry, Materials Science and Engineering, and Chemical Engineering, University of Toronto, 164 College St, Toronto, Ontario M5S 3G9, Canada.

    • Warren C. W. Chan
  4. Seiichi Ohta is at the Center for Disease Biology and Integrative Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–0033, Japan.

    • Seiichi Ohta
  5. Harold F. Dvorak is at the Center for Vascular Biology Research, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, Massachusetts 02215, USA.

    • Harold F. Dvorak

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The authors declare no competing interests.

Corresponding author

Correspondence to Warren C. W. Chan.

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